Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Infect Immun. 2011 Mar;79(3):1016-24. doi: 10.1128/IAI.00927-10. Epub 2010 Dec 13.
The regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. Orally ingested enterohemorrhagic Escherichia coli (EHEC) travels through the gastrointestinal tract and encounters a variety of environmental factors, some of which act as triggering signals for the induction of virulence genes. Butyrate, one of the main short-chain fatty acids (SCFAs), is such a signal, enhancing the expression of genes for intimate attachment and type III secretion. We further explored the role of SCFAs and found a positive effect of SCFAs on flagellar expression. Although EHEC did not produce flagella when grown in Dulbecco's modified Eagle's medium (DMEM), a tissue culture medium that enhances virulence gene expression, the addition of SCFAs to the medium induced the production of flagella, and the EHEC bacteria became motile. Among SCFAs, butyrate simultaneously activates both virulence and flagellar genes. Flagella did not affect initial adherence, and they were not expressed in adherent bacteria during microcolony formation. SCFAs activated flagellar genes via two regulatory steps. Butyrate activated the flhDC regulatory genes through leucine-responsive regulatory protein (Lrp), which is also a regulator of virulence genes. However, butyrate, acetate, and propionate also activated downstream genes independently of flhDC activation. Consequently, when encountering increased concentrations of SCFAs, which are abundant in acetate, in the intestine, EHEC first activates flagellar production and motility, followed by genes involved in adherence and type III secretion, which leads to efficient adherence in a preferable niche.
毒力基因的调控表达对于肠道病原体的成功感染至关重要。细菌依赖于感知环境信号来寻找更适宜的小生境并达到感染状态。经口摄入的肠出血性大肠杆菌（EHEC）在胃肠道中传播，并遇到各种环境因素，其中一些因素作为诱导毒力基因的触发信号。丁酸是主要的短链脂肪酸（SCFAs）之一，是这样的信号，增强了紧密附着和 III 型分泌的基因表达。我们进一步探索了 SCFAs 的作用，发现 SCFAs 对鞭毛表达有积极影响。尽管 EHEC 在杜氏改良伊格尔培养基（DMEM）中生长时不产生鞭毛，DMEM 是一种增强毒力基因表达的组织培养基，但向培养基中添加 SCFAs 会诱导鞭毛的产生，使 EHEC 细菌变得能动。在 SCFAs 中，丁酸同时激活毒力和鞭毛基因。鞭毛不会影响初始附着，并且在微菌落形成过程中，附着细菌不表达鞭毛。SCFAs 通过两个调节步骤激活鞭毛基因。丁酸通过亮氨酸响应调节蛋白（Lrp）激活 flhDC 调节基因，Lrp 也是毒力基因的调节剂。然而，丁酸、乙酸和丙酸也独立于 flhDC 激活而激活下游基因。因此，当在肠道中遇到大量的 SCFAs（乙酸中富含）时，EHEC 首先激活鞭毛的产生和运动，然后是参与附着和 III 型分泌的基因，从而在更适宜的小生境中有效地附着。
